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Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO2 responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial 133Xe clearance technique. The CO2 responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO2. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain O2 consumption was significantly higher during Sernylan analgesia (3.35 +/- 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 +/- 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.

Animals

Pulmonary and systemic hemodynamic effects of delta9-tetrahydrocannabinol in conscious and morphine--chloralose-anesthetized dogs: anesthetic influence on drug action.

Pulmonary and systemic hemodynamic effects of delta 9-tetrahydrocannabinol (delta 9-THC) in conscious dogs and in those anesthetized with morphine (3 mg/kg, i.m.) plus alpha-chloralose (100 mg/kg i.v.) were evaluated in this study. A decrease in the heart rate, cardiac output (PBF) and a concomitant increase in the pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) observed in conscious animals following the administration of delta 9-THC were qualitatively similar to the effects reported in dogs anesthetized with sodium pentobarbital; however, unlike in the pentobarbital group, hypotensive effects to THC were not evident in the consious animals. In contrast, the effect of delta 9-THC in morphine--chloralose dogs were different; in this group delta 9-THC administration resulted in increases in the heart rate the PBF, and significant reductions in PAR, PVR and RVSW. Further, a decrease in the arterial blood pressure noted following THC administration was closely associated with a reduction in the total peripheral resistance in the morphine--chloralose group. The results of this study indicated that the pulmonary effects of THC in dogs may be related to its actions on the heart rate and differ qualitatively as well as quantitatively depending on the anesthetic used.

Anesthetics

Renal vascular response to haemorrhage in the rabbit after pentobarbitone, chloralose-urethane and ether anaesthesia.

1. Total renal blood flow and its cortical distribution were measured by the microsphere technique before and after haemorrhage in conscious rabbits, and after haemorrhage in rabbits anaesthetized with pentobarbitone, chloralose-urethane or ether. 2. The average blood loss necessary to achieve a fall in systolic blood pressure to about 65 mmHg was 101 ml in conscious rabbits and 38, 90 and 118 ml in weight-matched groups of rabbits anaesthetized with pentobarbitone, chloralose-urethane and ether respectively. 3. After haemorrhage in conscious rabbits total renal blood flow fell by 25%, this fall being confined to the superficial renal cortex. 4. In rabbits subject to haemorrhage under pentobarbitone anaesthesia renal blood flow fell by a further 23% when compared with the conscious bled rabbits. This reduction in blood flow was confined to the superficial cortex. 5. Haemorrhage in the rabbits subjected to chloralose-urethane anaesthesia caused no significant change in renal blood flow, as compared with conscious bled rabbits. 6. Haemorrhage under ether anaesthesia was associated with a further 33% fall in total renal blood flow, as compared with conscious bled rabbits. This was associated with a fall of 32% and 34% in superficial and deep cortical blood flow respectively. 7. Animals subjected to general anaesthesia may be particularly susceptible to the renal haemodynamic effects of haemorrhage.

Anesthesia, General

The effects of pentobarbitone and chloralose anaesthesia on the vagal component of bronchoconstriction produced by histamine aerosol in the anaesthetized dog.

1 Total lung resistance (R(L)) and dynamic lung compliance (C(dyn)) were measured in dogs anaesthetized with pentobarbitone or chloralose and subjected to aerosols of histamine during 4 successive inspirations.2 Histamine caused concentration-dependent increases in R(L) and decreases in C(dyn). A significant vagal component was involved, but only when chloralose was employed and then only in the R(L) response.3 The resting values of R(L) and C(dyn) were similar regardless of which anaesthetic was used and remained essentially the same if the vagi were cooled.4 Electrical stimulation of the efferent vagi caused large increases in R(L) of dogs given chloralose and these effects were attenuated by the administration of pentobarbitone. Such stimulation was relatively ineffective in dogs given pentobarbitone alone.5In vitro, electrical field stimulation caused contractions of dog trachealis muscle. The responses were reduced by pentobarbitone in concentrations approximating to plasma levels in the anaesthetized dogs (1 to 5 x 10(-4) M), but the effects of exogenous acetylcholine were unaltered. The inhibition was dose-dependent, reversed by washing and unaltered by hexamethonium.6 The results suggest that pentobarbitone inhibits the vagal component of histamine-induced bronchoconstriction in the dog by an action on the efferent pathway. Furthermore, pentobarbitone acts either by blocking transmission along postganglionic parasympathetic nerves or by preventing the release of acetylcholine from the nerve endings in the lung.

Aerosols

Alterations in blood sugar, serum insulin and circulating free fatty acid responses to glucose load produced in dogs by chloralose anaesthesia.

The effects of chloralose anaesthesia on the BS, serum IRI and circulating FEA responses to glucose in dogs, in the course of glucose tolerance tests were studied. Chloralose induced a moderate glucose intolerance, and abolished both, the insulin response to hyperglycaemia in these animals and the lipolytic response at the end of the test. These effects indicate that chloralose anaesthesia is definitely improper for metabolic studied in experimental biology.

Anesthesia

[The effect of methohexital, fentanyl, droperidol, and chloralose on the aortic baroceptor discharge of decerebrated cats (author's transl)].

The effect of methohexitone, fentanyl, droperidol and chloralose on the response characteristics of aortic barorecptors was studied in decerebrated cats. The conclusions rest on the analysis of the drug effect on the stimulus-response curves of individual baroceptor fibres of the aortic region relating the average discharge rate (spike/s) to the average aortic arch pressure which was altered over wide ranges by a balloon catheter located in the thoracic aorta. The stimulus response curves were shifted to higher activities by methohexitone and less obviously also by droperidol. Contrarywise, chloralose and fentanyl shifted these curves to lower activities. Thus, the first two drugs increase the afferent receptor drive and favour the development of arterial hypotension, whereas the last two decrease the afferent receptor drive and act to stabilize the arterial pressure. Interestingly, at comparable depth of anesthesia arterial blood pressure levels tend to be lower with the first kind of anaesthetics as compared with the last.

Animals

Chloralose induced alteration of visually evoked response from specific and non-specific regions of cat neocortex.

Visually evoked response (VER) and EEG from the motor cortex (precruciate gyrus) and the visual cortex (marginal gyrus) of cats were recorded from 4 to 7 h after the injection of anesthetic doses of alpha-chloralose. During the recording period the VER from the precruciat gyrus showed a 200-300% increase in amplitude while the VER from the marginal gyrus rarely varied more than 50% in amplitude, and did so independent of the changes in the VER from the precruciate gyrus. The number of large amplitude spikes in the EEG from the precruciate gyrus also increased dramatically during the recording period, but no definite correlation between changes in VER amplitude and in the number of spikes in the EEG could be demonstrated. These observations suggest a functional separation between specific and nonspecific sensory pathways, with the latter showing a considerably greater sensitivity to level of anesthesia.

Animals

Central cardiovascular effects of phentolamine in chloralose-anesthetized cats.

Phentolamine (50, 100 and 200 microng/min for 30 min) perfused through the cerebroven system of chloralose-anesthetized cats produced dose-related reductions in tricular blood pressure. Evidence is presented which suggests that this hypotensive activity was due to an interaction at central nervous system sites and was not attributable to escape of the compound from the brain. Centrally administered phentolamine was more effective in lowering blood pressure than the i.v. infusion of phentolamine at a dose (25 microng/kg/min for 30 min) which markedly antagonized peripheral alpha-adrenoceptors. In addition, central phentolamine induced bradycardia in contrast to the tachycardia which accompanied i.v. administration. By limiting the perfusion of phentolamine to selected portions of the cerebrospinal fluid spaces a major site of action responsible for the hypotensive activity was located outside the ventricles in an area accessible from the subarachnoid spaces. A second, less important site, anterior to the midbrain adjacent to the ventricular system apparently contributed to the hypotension. Phentolamine, introduced centrally, also impaired reflexogenic bradycardia elicited by pressor doses of norepinephrine. Both the sympathetic withdrawal and the vagal activation which account for this reflex seemed to be antagonized by phentolamine.

Anesthesia

Intrathecal tolerance of metrizamide in chloralose anesthetized cats.

The water soluble radiopaque medium, metrizamide (Amipaque) was introduced into the lumbar subarachnoid space in chloralose anesthetized cats at a standard volume of 0.35 cc/kg in concentrations of 300 mgI/cc to 500 mgI/cc during EMG recording. These animals did not differ from controls which received cerebrospinal fluid under otherwise identical conditions; both groups usually showed some mild and occasional muscle fasciculations or mild spasms. Treatment with metrizamide appeared to be a less deleterious procedure than that using hyperosmotic sucrose (1.32 M) as judged from EMG records. In contrast, equivalent amounts of neglumine iothalamate produced frank convulsions in 7 of 15 cases and a range of hyperirritability in the remaining 8.

Anesthesia

Discharge patterns of Purkinje cells in cats anaesthetized with alpha-chloralose.

1. Micro-electrodes have been used to record from 119 Purkinje (P) cells in the paramedian lobule of the cerebellum in cats anaesthetized with alpha-chloralose. 2. The spontaneous discharge rate and degree of irregularity of the discharge varied very much from one cell to another; the over-all mean rate (about 25/sec) was a little lower than has been reported either for barbiturate anaesthetized or for decerebrate unanaesthetized preparations. 3. Following electrical stimulation of a peripheral nerve, most P cells responded with both simple spikes and a climbing fibre response. This initial response was usually succeeded by a prolonged period of silence (over-all mean duration 350 msec) before resumption of the tonic simple spike discharge. Similar response-silence sequences could also be evoked by mechanical stimulation such as a tap applied to the pads of the forepaw. 4. Electrical stimulation of the inferior olive evoked climbing fibre responses followed by a prolonged pause in the simple spike discharge of the cell. 5. In six individual preparations, recordings were made both from P cells of the paramedian lobule and from neurones of nucleus interpositus (to which the former project). Comparison of the responses of the two types of neurone to peripheral nerve and inferior olivary stimulation showed that the end of the pauses in P cell firing correlated well with the end of a prolonged period of facilitation of the interpositus neurones. 6. These results support the hypothesis advanced in an earlier report (Armstrong, Cogdell & Harvey, 1975) that the prolonged facilitatory responses of interpositus neurones are essentially disinhibitory responses resulting from reduction in the activity of overlying cells, and that responses of P cells and of interpositus neurones consist, in general, of modulations of activity which are mutually out of phase.

Action Potentials

The response of three strains of fowl to alpha-chloralose.

A heavy and two light strains of pullets suffered a decline in egg production but an improvement in body weight gains when alpha-chloralose, a tranquilizer, was included in their diets at .1 to .3%. Feed efficiency also experienced a decline while egg size and Haugh unit were not affected.

Animals

Electrocerebral changes in acute alpha-chloralose poisoning: a case report.

A patient who had swallowed a high dose of alpha-chloralose (AC) exhibited a severe CNS depression, myoclonic convulsions and a flat EEG tracing. An episode of respiratory depression occurred also during hospitalization. The cerebral electrical activity reappeared after 18 hrs., EEG and clinical pictures subsequently showing a rapid improvement. Chemical tests revealed the presence of 0.3 mg/100 ml of trichloroethanol in the blood. Treatment included the administration of diazepam against convulsions and assisted respiration. This case confirms previous clinical and experimental observations, proving that AC should be regarded as a convulsant in addition to being an anesthetic agent.

Chloralose

Intraventricular infusion of angiotensin II on the hemodynamics and renal function of alpha-chloralose anesthetized cats.

Intraventricular infusion of angiotensin II (50, 100, and 200 ng/kg per min) produced significant elevations of arterial blood pressure (20-25%) in alpha-chloralose-anesthetized cats. The pressor responses were not accompanied by significant changes in heart rate,cardiac output, or contractility and were chiefly due to significant increases in total peripheral resistance. In contrast, pressor responses to intravenous infusion of angiotensin II (100 ng/kg per min) were accompanied by reflex decrease in cardiac activity. While intravenous angiotensin II caused increases in the resistance of skeletal, mesenteric, and renal vasculature, the intraventricular administration of angiotensin II increased resistance only in the mesenteric and renal vasculature. Further, centrally administered angiotensin II significantly enhanced urinary output and the rate of Na+ excretion both in the intact as well as in the denervated kidneys. However, the diuretic and natriuretic effects were significantly greater in the intact than in the denervated kidneys, indicating a centrally mediated neurogenic mechanism. The significant increase in the urinary concentration of Na+ (mEq/liter) following intraventricular angiotensin appeared to be secondary to the elevation of arterial blood pressure, since this effect was unaltered by acute renal denervation. The results of this investigation are consistent with the hypothesis that an elevation in the concentration of angiotensin II within the cerebrospinal fluid may trigger neurogenic mechanisms resulting in the constriction of glomerular efferent arterioles. Such an effect would be expected to increase glomerular filtration pressure and filtration fraction, and may play a role in the diuretic and natriuretic effects noted.

Anesthesia, General

Central cardiovascular effects of SQ 14,225, an angiotensin-converting enzyme inhibitor in chloralose-anesthetized cats.

Experiments were conducted in chloralose-anesthetized cats to investigate the central and peripheral cardiovascular effects of a new orally active angiotensin-converting inhibitor, SQ 14,225 (3-mercapto-2-D-methylpropanoyl-L-proline). I.v. administration of SQ 14,225 (0.31-3100 microgram/kg) antagonized the pressor responses to angiotensin I (AI) (310 ng/kg) i.v. in a dose-related manner but did not alter responses to angiotensin II (AII) (200 ng/kg) i.v. Similarly, intracerebroventricularly (i.c.v.) administered SQ 14,225 (0.31-310 microgram/kg perfused over 10 min) produced dose-related decreases in the centrally mediated pressor responses and heart increases elicited by AI (310 ng/kg) i.c.v. The central responses to AII (200 ng/kg) i.c.v. were not affected by SQ 14,225. Passage of SQ 14,225 out of the ventricular system into the systemic circulation was detected, but only at doses greater than that required to antagonize central AI responses. Doses of SQ 14,225 (310 microgram/kg and 3.1 mg/kg) i.v. which maximally inhibited i.v. AI responses, had no effect upon central AI activity. This finding suggests that passage of SQ 14,225 across the blood brain barrier into the central nervous system is restricted. Peripheral or central administration of SQ 14,225 produced only minimal transient decreases in blood pressure (less than 10 mm Hg). The results of these studies indicate that SQ 14,225 is a potent inhibitor of AI conversion in the brain as well as in the peripheral circulation.

Angiotensin I

Cardiovascular effects of morphine and opioid peptides following intracisternal administration in chloralose-anesthetized rats.

Beta-Endorphin (0.9--2.0 nmol), morphine (11--250 nmol) and D-ala2-met-enkephalinamide (17--33 nmol) administered intracisternally produced preferential vasodepressor responses and bradycardia. Leu- (1.8--180 nmol), met-enkephalin (17--520 nmol) and alpha-endorphin (5.7--57 nmol) administered in the same way produced preferential vasopressor effects and the latter two peptides also produced bradycardia. Results obtained with naloxone (300 nmol) given intracisternally indicate that the pressor and depressor actions as well as the bradycardia are mediated through opiate receptors. The results indicate that opioid peptides may be involved in central cardiovascular control.

Anesthesia